1α,25‐dihydroxyvitamin D₃ Inhibits Adipocyte Mediated Metastatic Capability of Breast Cancer Cells

Abstract

Excess adiposity is thought to be associated with approximately 20% of all cancers, including breast cancer. However the mechanism underlying this relationship remains controversial. Adipocytes secrete a wide array of bioactive molecules which act as key mediators in several obesity‐associated diseases. Further, the active form of vitamin D, 1α,25dihydroxyvitamin D (1,25(OH)2D) regulates multiple aspects of adipocyte biology, including adipogenesis and adipocyte apoptosis, as well as modulating the release of factors associated with cancer promotion. The purpose of these studies was to investigate 1,25(OH)2D‐mediated regulation of differentiated adipocytes to determine the impact on breast cancer progression. Differentiated 3T3‐L1 adipocytes were treated with 1,25(OH)2D (10 nM) for 2 days, followed by harvesting the adipocytes and collection of adipocyte conditioned media (ACM). ACM from adipocytes treated with 1,25(OH)2D decreased cell proliferation in metastatic MDA‐MB‐231 and MCF10CA1a cells compared to vehicle treated ACM, (42% and 37% of vehicle ACM, respectively), as measured by an MTT assay. In addition, ACM from adipocytes treated with 1,25(OH)2D inhibited cell migration and wound healing in MDA‐MB‐231 cells (37% and 30% respectively relative to vehicle ACM). In order to explore the mechanism underlying these effects on breast cancer metastatic capability, the mRNA expression of IGF‐1, IL‐6 and leptin was measured in adipocytes treated with either vehicle or 1,25(OH)2D. Treatment of adipocytes with 1,25(OH)2D decreased mRNA expression of IGF‐1, IL‐6 and leptin by 23%, 85%, and 39%, respectively. Further studies aim at demonstrating the mechanism underlying the impact of 1,25(OH)2D on adipocytes to inhibit their capability of promoting breast cancer metastasis. In summary, these results suggest that 1,25(OH)2D alters adipocyte secretions to inhibit breast cancer metastasis.Support or Funding InformationThis work was supported in part by the Higher Education Challenge Grant from the National Institute of Food and Agriculture, United States Department of Agriculture (#2013‐70003‐20922).